Swine Flu: How the H1N1 Virus Got Its Start

Around Thanksgiving 2005 a teenage boy helped his brother-in-law butcher 31 pigs at a local Wisconsin slaughterhouse, and a week later the 17-year-old pinned down another pig while it was gutted. In the lead-up to the holidays the boy's family bought a chicken and kept the animal in their home, out of the harsh Sheboygan autumn. On Dec. 7, the teenager came down with the flu, suffering an illness that lasted three days. He visited a local clinic, then fully recovered, and nobody else in his family took ill.

This incident would hardly seem worth mentioning except that the influenza virus that infected the Wisconsin lad was unlike any previously seen. It appeared to be a mosaic of a wild-bird form of flu, a human type and a strain found in pigs.

It was an H1N1 swine influenza. Largely ignored at the time, the Wisconsin virus was a step along the evolutionary tree, leading to a virus that four years later would stun the world.

Flash-forward to April 2009, and young Édgar Enrique Hernández in faraway La Gloria, Mexico, suffers a bout of flu, found to be caused by a similar mosaic of swine/bird/human flu, also H1N1. And thousands of miles away in Cairo, the Egyptian government decides pigs are the source of disease, and orders 300,000 animals in the predominantly Muslim (therefore not pork-consuming) society slaughtered.

Each of these three incidents is related to the unfolding influenza crisis. It is the manner of human beings to seek blame during times of fear. Fingers are now pointing, either at the entire pig species Sus domestica, or at the nation of Mexico. Such exercises in blame are not only scientifically ill founded, ut are likely to prompt government actions that, at the very least, are useless and, at worst, harmful for efforts to control a pandemic.

We live in a globalized world, filled with shared microbial threats that arise in one place, are amplified somewhere else through human activities that aid and abet the germs, and then traverse vast geographic terrains in days, even hours—again, thanks to human activities and movements. If there is blame to be meted out, it should be directed at the species Homo sapiens and the manifest ways in which we are reshaping the world ecology, offering germs like the influenza virus extraordinary new opportunities to evolve, mutate and spread.

Back in 2005, the Wisconsin Division of Public Health hunted for sick pigs in Sheboygan County, but the animals the teenager had helped slaughter came from multiple farms across the area, and every farmer claimed his herd was healthy. The Wisconsin authorities forwarded blood samples from the infected teenager and his family to the Centers for Disease Control and Prevention in Atlanta. The CDC scientists discovered that the H1N1 virus had pieces of its RNA genetic material that matched a human flu first seen in New Caledonia in 1999, two swine types that had been circulating in Asia and Wisconsin for several years and an unknown avian-flu virus.

In 2006 the American Association of Swine Veterinarians reported that humans were passing their H1N1 viruses to pigs, causing widespread illness in swine herds, especially in the American Midwest. A year later at a county fair in Ohio an outbreak occurred, sickening many of the pigs, but not their human handlers. The cause was a type of H1N1 that was a close match to the Wisconsin strain, and may have been spread from human to pig.

Last year researchers from Iowa State University in Ames warned that pigs located in industrial-scale farms were being subjected to influenza infections from farm poultry, wild birds and their human handlers. Writing in The Journal of Infectious Diseases, Eileen Thacker and Bruce Janke said, "As a result of the constantly changing genetic makeup of individual influenza viruses in pigs, the U.S. swine industry is continually scrambling to respond to the influenza viruses circulating within individual production systems."

Something was changing. Pigs notoriously eat just about anything thrown their way, and rub up against each other frequently, readily passing infections within herds. Their stomachs are remarkably tolerant environs for microbes, which since ancient times have caused illness in humans who dined on raw or undercooked pork. Investigation of the 1918 influenza pandemic, which is now estimated to have killed up to 100 million people worldwide in 18 months, revealed that the viral culprit was a type H1N1 human flu that had infected pigs, and then circulated back to humans.

At the viral level, influenza is an awfully sloppy microbe that is in a constant state of mutation and evolution. Its genetic material is in the form of RNA (not DNA, as in humans), loosely collected into chromosomes. When a virus infects a cell, its chromosomes essentially fall apart into a mess, which is copied to make more viruses that then enter the bloodstream to spread throughout the body. Along the way in this copying process any other genetic material that may be lying about the cell is also stuffed into the thousands of viral copies that are made. If the virus happens to be reproducing this way inside a human cell, it picks up Homo sapiensgenetic material; from a chicken cell it absorbs avian genes; and from a pig cell it garners swine RNA. The jackpot events in influenza evolution occur when two different types of flu viruses happen to get into an animal cell at the same time, swapping entire chromosomes to create "reassorted" viruses.

What was infecting that teenager in Sheboygan was a triple reassortment, resulting in a new virus with bits of genes from three species of animals—one of them Homo sapiens.

But who pays attention to such things? Other than vets, pig farmers and the occasional virologist, not many people in public health, government or medicine usually give much thought to the four-legged viral mixing vessels that oink their way around family farms and vast industrial pork-production centers. Thacker and Janke's 2008 writing seems sadly prescient today: "Pigs would be an ideal mixing vessel for the creation of new avian/mammalian influenza viruses capable of causing novel diseases with the potential for producing pandemics in the human population … It is apparent that, in the U.S. swine industry, transmission of influenza viruses between swine and humans is fairly common and is bidirectional."

Nine months ago the Texas Department of State Health Services reported the case to the CDC of an individual who was exposed to ailing pigs. The Texan came down with flu, spread it to no one and was fine after a few days. In the patient's blood, CDC scientists found "a swine influenza A (H1N1) triple reassortant virus, A/Wisconsin/87/2005 H1N1," the same virus that infected the Sheboygan teenager three years earlier.

And then, this March, the outbreak of 2009 commenced. It might not have been noticed, frankly, if things unfolded in the same bird/human/swine manner as had previously evoked only humdrum attention in Wisconsin, Ohio and Texas. But this time, people died.

In mid-March the number of routinely reported influenza cases in several Mexican states suddenly spiked upward. At roughly the same time, public-health authorities in southern California spotted two separate cases of flu in children: a 10-year-old boy in San Diego County, and a 9-year-old girl in Imperial County. Though both children survived their illnesses, there was evidence that it had spread to family members, and samples of the children's blood were examined at the CDC in early April. Bingo: H1N1 triple-reassorted influenza. Meanwhile, in Mexico, more than 50 serious flu cases emerged over the same time period, and the government forwarded blood samples to Canada's top infectious-diseases lab in Winnipeg. The Canadians confirmed that the Mexican mystery virus was H1N1, and the potential pandemic saga unfolded.

In Mexico, attention has focused on little Édgar Enrique Hernández, who is believed to have come down with the new flu on April 2. The blame for Hernández's infection is aimed at an American-owned industrial pig center located near the child's home in La Gloria. Residents had long complained about the stench and dust from the plant, and have eagerly named it as the source of the child's infection. It may be true that Hernández inhaled H1N1 from a pig, but because other cases emerged in March, the timing of the case is off: Édgar Hernández is not Patient Zero in the outbreak of 2009.

This virus has been evolving for a long time, no doubt aided in its transformation by the ecology of industrial-scale pig farming in North America. Some scientists say there are genetic elements in the virus that date back to an Indiana pig farm in 1987. In that sense, it is similar to the "bird flu," or H5N1, which surfaced in wild migratory water birds in southern China some time in the early 1990s and infected people in Hong Kong in 1997. As that virus has evolved over the past 12 years, it has taken advantage of large poultry farms, and major bird-migration centers, to spread rapidly and absorb new genetic material along the way. In 2005, as H5N1 spread to Siberia and Europe, the United Nations and the Bush administration mobilized cash, scientific expertise and the needed infrastructure to find and contain outbreaks, primarily by slaughtering infected chicken flocks.

In Indonesia, where the virus has spread to pigs and humans, it appears H5N1 can be passed, in rare cases, between people, and human infection is an extraordinarily dangerous event: 82 percent of infected Indonesians have succumbed to the flu virus. The global average mortality rate for H5N1 in people is 63 percent, which makes it one of the most fearsome microbes on earth.

Here, then, is where we stand.

We have a new virus in the world that appears to be very contagious between people, and possibly between swine and humans. It is, fortunately, treatable with the antiviral drugs Tamiflu and Relenza (oseltamivir and zanamivir), but it is resistant to the other major class of anti-flu drugs, amantadines. It is still evolving, and moving, and its ultimate trajectory cannot be seen right now. We do not yet know how deadly this virus is: while Mexico has been able to track down the numbers of dead and hospitalized H1N1 cases, it cannot determine just how many Mexicans have been infected with the virus since it started spreading there in late March. It's one thing to say that 150 people out of, perhaps, 10 million infected have died: that gives you a case fatality rate that is roughly what we see with normal, seasonal flu. (Each year, seasonal flu kills 36,000 people in the United States alone.) It's quite another story if Mexico's denominator is 5,000, for a case fatality rate of 3 percent--a full percentage point worse than the rate seen with the 1918 influenza. It is urgent that we discern the denominator.

We have a second, closely related H1N1 human virus in circulation around the world. Though widespread, it is not unusually lethal. Last year this virus developed full resistance to Tamiflu. It would be most disturbing if the 2008 H1N1 human virus were to reassort with the new swine/human virus, as we could then be facing a more drug-resistant pandemic strain of influenza, treatable only with the drug Relenza, which must be administered with an inhaler device.

We have a third, older pandemic in poultry, occasionally infecting humans, that involves the H5N1 virus. This pandemic has circulated long enough so that the virus has branched into several evolutionary trees, including forms that are drug-resistant. In Egypt, where it is common for urban families to raise chickens in their yards, H5N1 has caused a significant number of human cases, and its spread appears to be uncontrolled. The World Health Organization (WHO) is distressed by evidence that H5N1 is becoming less deadly for people. That could mean that the bird-flu virus is evolving toward a less-lethal form that is more capable of spreading between people.

It is supremely ironic, then, that the Egyptian government in late April started slaughtering the nation's 300,000 pigs as an alleged flu-control measure. The swine form of H1N1 may not be in Egypt as of this writing, but the chicken H5N1 most definitely is, and has to date infected 68 Egyptians, killing 23. Egypt has never carried out wholesale slaughter of poultry, as chicken is a staple of the national diet. Pork, in contrast, is consumed only by the minority Christian population. An Egyptian Islamist group has declared that swine flu is "God's revenge against infidels."

The Muslim Brotherhood in Egypt recently declared that the Cairo-based U.S. Naval Medical Research Unit (NAMRU), which has provided public-health work for the entire Middle East for decades, must be shut down, and Egypt must stop sending samples of H5N1 viruses that emerge in the country to the WHO. The Egyptian group, which holds seats in Parliament, is echoing sentiments first put forward by Indonesia's minister of health, Siti Supari, who has refused to share her country's H5N1 samples with the WHO since 2006. Supari is also trying to evict another NAMRU lab from Jakarta. On April 28, Supari declared that the new swine flu was genetically engineered and released in order to promote American pharmaceutical sales worldwide.

Two days later, Supari denied making such statements, though they were con-sistent with her longstanding claim that rich countries--particularly the United States--prey on poorer nations in the interest of drug-company profits. In heated negotiations with the World Health Organization and the U.S. government, Supari has insisted on the existence of "viral sovereignty," wherein nations own any viruses that they discover within their boundaries, have the right to refuse sharing them with the WHO or any other foreign entity and may demand all profits derived from vaccines and other products made from those viruses. Under this principle, Indonesia refuses to allow the outside world access to at least 50 H5N1 strains thought to have emerged in that country since 2005. Without access to the various viral strains, scientists cannot tell if H5N1 is evolving dangerous attributes in Indonesia, or whether the hideously high death rate in infected people there is due to some unique viral characteristics. Therefore, the principle of viral sovereignty directly imperils the entire global community--as well as Supari's own people. On April 30, the WHO repudiated another Supari claim: that Indonesians have special genetic or environmental traits that would keep them safe from the new swine flu.

Happily, Mexico has shown the world how a responsible nation can respond to a potential pandemic. By moving swiftly to shut down schools, entertainment and places of social congregation, Mexico—an already beleaguered economy—is facing dire financial consequences. But its dramatic actions may be saving Mexican lives, and slowing down the outbreak of 2009. In that sense, the world owes Mexico a big gracias.

Governments the world over would do well to pay attention to Mexico's response, and learn from it. Throughout Asia, governments have been pulling their old SARS-epidemic thermal monitors out of mothballs, and scanning people for evidence of fevers. That worked for SARS control because the SARS virus was almost exclusively contagious when people were running fevers. Not so with influenza: flu can be very contagious before the individual carrier has any symptoms at all, much less a fever.

Worse, some governments are banning pork products from the Americas, as if it were possible to get the flu from eating a cooked sausage. It is not.

A wiser set of pig-related actions would turn to the strange ecology we have created to feed meat to our massive human population. It is a strange world wherein billions of animals are concentrated into tiny spaces, breeding stock is flown to production sites all over the world and poorly paid migrant workers are exposed to infected animals. And it's going to get much worse, as the world's once poor populations of India and China enter the middle class. Back in 1980 the per capita meat consumption in China was about 44 pounds a year: it now tops 110 pounds. In 1983 the world consumed 152 million tons of meat a year. By 1997 consumption was up to 233 million tons. And the United Nations Food and Agriculture Organization estimates that by 2020 world consumption could top 386 million tons of pork, chicken, beef and farmed fish.

This is the ecology that, in the cases of pigs and chickens, is breeding influenza. It is an ecology that promotes viral evolution. And if we don't do something about it, this ecology will one day spawn a severe pandemic that will dwarf that of 1918.